The present invention relates to the field of medicine, and in some embodiments to devices and compositions comprising a leptin antagonist formulated for localized release of a leptin antagonist at the site of treatment as well as methods of using such compositions for treating disorders, including cardiovascular disorders.
Cardiovascular disease (CVD) is a class of diseases that involve the heart and/or the blood vessels. Several studies have related inflammatory markers to cardiovascular disease (CVD) and several assays for inflammatory markers are commercially available. For example, C-reactive protein (CRP), a common inflammatory marker, has been found to be present in increased levels in patients who are at risk for cardiovascular disease [Karakas and Koenig, 2009 Herz 34 (8); 607-13] while osteoprotegerin, which is involved with regulation of NF-κB, has been found to be a risk factor for cardiovascular disease and mortality [Venuraju et al., 2010 J. Am. Coll. Cardiol. 55 (19): 2049-61].
As a result of these findings, the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly. However, to date there is no consensus among professionals as to how these markers of inflammation should be used as a basis for clinical treatment.
Although it has been shown that some cardiovascular disorders can benefit from suppression of inflammation-related processes and cellular proliferation as part of a remodeling response (e.g. use of locally released cytotoxic drugs such as paclitaxel or sirolimus in preventing restenosis or use of doxycycline in treatment of abdominal aortic aneurysm (AAA)), to date, there is no evidence to suggest that cardiovascular disease can benefit from anti-inflammatory treatment.
Leptin is a naturally occurring pleiotropic molecule that regulates food intake as well as metabolic and endocrine functions. Leptin also plays a regulatory role in immunity, inflammation, and hematopoiesis.
The human leptin precursor is a linear polypeptide 167 amino acid residues long represented by NCBI Reference Sequence NP_000221.1 (SEQ ID NO 1) encoded by the mRNA having the nucleotide sequence NCBI Reference Sequence NM_000230. Residues 1-21 of the sequence constitute the signal peptide while residues 22-167 constitute the mature hormone.
Leptin antagonists are also known, see for example, U.S. Pat. Nos. 7,307,142 and 8,969,292.